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1.
Urology ; 136: 238-240, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31758979

RESUMO

Menkes disease, or Kinky Hair Syndrome, is a rare disorder of copper metabolism that causes fatal neurodegenerative disease in infancy. This X-linked disorder results from mutations in the ATP7A gene. Along with neurological decline, characteristic coarse appearance of the hair is seen. Urological issues are prevalent in this patient population, with bladder diverticula being the most common. Herein, we describe a unique male patient with genetic mosaicism and osseous metaplasia found in a ruptured bladder diverticulum.


Assuntos
Doenças Ósseas/etiologia , Doenças Ósseas/patologia , Osso e Ossos/patologia , Divertículo/complicações , Síndrome dos Cabelos Torcidos/complicações , Bexiga Urinária/anormalidades , Criança , Humanos , Masculino , Síndrome dos Cabelos Torcidos/genética , Metaplasia/etiologia , Mosaicismo
2.
Yakugaku Zasshi ; 139(12): 1495-1500, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31787635

RESUMO

The roles of chondroitin sulfate (CS) and dermatan sulfate (DS) have been demonstrated in various biological events such as the construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, and growth factors. Human genetic diseases, including skeletal abnormalities, connective tissue diseases, and heart defects, were reported to be caused by mutations in the genes encoding glycosyltransferases, epimerases, and sulfotransferases that are responsible for the biosynthesis of CS and DS. Glycobiological approaches revealed that mutations in CS- and DS-biosynthetic enzymes led to reductions in their enzymatic activities and in the levels of CS and DS. Furthermore, CS at the surface of tumor cells plays a key role in pulmonary metastasis. A receptor for advanced glycation end-products (RAGE) was predominantly expressed in the lung, and was identified as a functional receptor for CS chains. CS and anti-RAGE antibodies inhibited the pulmonary metastasis of not only Lewis lung carcinoma but also B16 melanoma cells. Hence, RAGE and CS are potential targets of drug discovery for pulmonary metastasis and a number of other pathological conditions involving RAGE in the pathogenetic mechanism. This review provides an overview of glycobiological studies on characterized genetic disorders caused by the impaired biosynthesis of CS, as well as DS, and on the pulmonary metastasis of Lewis lung carcinoma cells involving CS and RAGE.


Assuntos
Doenças Ósseas/etiologia , Doenças Ósseas/genética , Carcinoma Pulmonar de Lewis/etiologia , Carcinoma Pulmonar de Lewis/secundário , Condroitina/biossíntese , Dermatan Sulfato/biossíntese , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/secundário , Receptor para Produtos Finais de Glicação Avançada , Dermatopatias/etiologia , Dermatopatias/genética , Animais , Carcinoma Pulmonar de Lewis/genética , Humanos , Neoplasias Pulmonares/genética , Camundongos , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo
3.
Medicine (Baltimore) ; 98(51): e18431, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861011

RESUMO

The aim of this study was to measure the urate volume within tophus and bone erosion volume using dual-energy computed tomography in patients with tophaceous gout. Furthermore, our study aims to quantitatively analyze the relationship between monosodium urate (MSU) crystal deposition and bone erosion according to the anatomic location of urate deposition.Seventy-seven subjects with chronic gout were positively identified for the presence of urate deposition. Only 27 subjects identified for the presence of urate in contact with bone erosion were included in this study. The urate volumes and associated erosion volumes were measured. The relationships between urate within tophus and bone erosion were separately analyzed according to the anatomic location of urate deposition.Twenty-seven subjects were all male (100%) with a median (interquartile range, IQR) age of 52 (45-61) years. From all the subjects, 103 tophi depositions were identified in contact with bone erosion, including 58/103 tophi that contained an intraosseous component and 45/103 nonintraosseous tophi. Tophi containing intraosseous components were larger than nonintraosseous tophi (urate volume: median [IQR] 45.64 [4.79-250.89] mm vs 19.32 [6.97-46.71] mm, P = .035) and caused greater bone erosion (erosion volume: 249.03 [147.08-845.33] mm vs 69.07 [32.88-111.24] mm, P < .001). Almost all erosion volumes were larger than urate volumes in nonperiarticular tophi, in contrast to most erosion volumes, which were less than urate volumes in the tophi that contained a periarticular component (odds ratio, 95% confidence interval: 74.00, 14.70-372.60; P < .001). Urate volume and erosion volume demonstrated positive correlations in intraosseous tophi, intraosseous-intra-articular-periarticular tophi, and intraosseous-intra-articular tophi (rs = 0.761, rs = 0.695, rs = 0.629, respectively, P < .05).MSU crystal deposition shows a promoting effect on the development of bone erosions in varying degrees, associated with the location of MSU crystals deposited in the joints. The intraosseous tophi contribute the most to bone erosions, followed by intra-articular tophi, and periarticular tophi.


Assuntos
Doenças Ósseas/etiologia , Gota/complicações , Ácido Úrico/metabolismo , Adulto , Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/metabolismo , Gota/diagnóstico por imagem , Gota/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
4.
Nat Commun ; 10(1): 4533, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586071

RESUMO

Multiple myeloma is an incurable, bone marrow-dwelling malignancy that disrupts bone homeostasis causing skeletal damage and pain. Mechanisms underlying myeloma-induced bone destruction are poorly understood and current therapies do not restore lost bone mass. Using transcriptomic profiling of isolated bone lining cell subtypes from a murine myeloma model, we find that bone morphogenetic protein (BMP) signalling is upregulated in stromal progenitor cells. BMP signalling has not previously been reported to be dysregulated in myeloma bone disease. Inhibition of BMP signalling in vivo using either a small molecule BMP receptor antagonist or a solubilized BMPR1a-FC receptor ligand trap prevents trabecular and cortical bone volume loss caused by myeloma, without increasing tumour burden. BMP inhibition directly reduces osteoclastogenesis, increases osteoblasts and bone formation, and suppresses bone marrow sclerostin levels. In summary we describe a novel role for the BMP pathway in myeloma-induced bone disease that can be therapeutically targeted.


Assuntos
Doenças Ósseas/tratamento farmacológico , Proteínas Morfogenéticas Ósseas/metabolismo , Mieloma Múltiplo/complicações , Pirazóis/farmacologia , Pirimidinas/farmacologia , Células-Tronco/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas/etiologia , Doenças Ósseas/patologia , Medula Óssea/patologia , Receptores de Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Receptores de Proteínas Morfogenéticas Ósseas/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Fêmur/citologia , Fêmur/efeitos dos fármacos , Fêmur/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos , Mieloma Múltiplo/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/patologia , Tíbia/citologia , Tíbia/efeitos dos fármacos , Tíbia/patologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Dis Markers ; 2019: 9417914, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485281

RESUMO

Bone remodeling represents a physiological phenomenon of continuous bone tissue renewal that requires fine orchestration of multiple cell types, which is critical for the understanding of bone disease but not yet clarified in precise detail. Exosomes, which are cell-secreted nanovesicles drawing increasing attention for their broad biosignaling functions, can shed new light on how multiple heterogeneous cells communicate for the purpose of bone remodeling. In the healthy bone, exosomes transmit signals favoring both bone synthesis and resorption, regulating the differentiation, recruitment, and activity of most cell types involved in bone remodeling and even assuming an active role in extracellular matrix mineralization. Additionally, in the ailing bone, they actively participate in pathogenic processes constituting also potential therapeutic agents and drug vectors. The present review summarizes the current knowledge on bone exosomes and bone remodeling in health and disease.


Assuntos
Doenças Ósseas/etiologia , Remodelação Óssea , Exossomos/metabolismo , Animais , Humanos , Osteogênese
6.
BMJ Case Rep ; 12(8)2019 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-31383675

RESUMO

Hypercalcaemia, renal dysfunction, anaemia and bone lesions (CRAB) are a constellation of signs and symptoms that are collectively referred to as the CRAB features. When present together, multiple myeloma (MM) should be at the top of the differential diagnosis. We present a 69-year-old man who presented with severe body aches and bone pain in his ribs and pelvis, associated with fatigue and constipation. He was found to have hypercalcaemia, acute kidney injury, anaemia and numerous lytic lesion on chest imaging. Physical examination and imaging were unremarkable for any enlarged lymph nodes. The patient was initially suspected to have multiple myeloma, however, serum and urine protein electrophoresis, and serum free light chain assays were negative. The patient was ultimately diagnosed with diffuse large B cell lymphoma based on a bone marrow biopsy. This case highlights the fact that presence of hypercalcaemia, renal dysfunction, anaemia and bone lesions are not usually specific for MM.


Assuntos
Anemia/diagnóstico , Doenças Ósseas/diagnóstico , Hipercalcemia/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Insuficiência Renal/diagnóstico , Idoso , Anemia/etiologia , Doenças Ósseas/etiologia , Diagnóstico Diferencial , Humanos , Hipercalcemia/etiologia , Linfoma Difuso de Grandes Células B/complicações , Masculino , Mieloma Múltiplo/diagnóstico , Insuficiência Renal/etiologia
7.
J Zoo Wildl Med ; 50(2): 437-446, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260211

RESUMO

Hypertrophic osteopathy, a syndrome characterized by painful distal limb swelling and proliferative periosteal reaction, primarily involves the metacarpal and metatarsal bones and phalanges. Lesions are often bilaterally symmetric and typically affect all four limbs. Hypertrophic osteopathy is frequently associated with primary intrathoracic disease, though this condition has also been reported secondary to intra-abdominal and intrapelvic disease and associated with pregnancy in both people and horses. Over a 20-yr period, five adult female Sichuan takin (Budorcas taxicolor tibetana), with 13 total pregnancies, were evaluated because of lameness and distal limb swelling. These clinical signs were observed between 2 and 32 days (mean = 19 days) prior to parturition (gestation period in takin approximately 200-240 days) and resolved in all animals following parturition. Lameness and limb swelling resolved between 8 and 168 days (median = 15 days) after parturition. Sixteen radiographic examinations, from four of the individuals, documented proliferative periosteal reaction, primarily of the metacarpal bones, metatarsal bones, and phalanges. The clinical progression, resolution of signs, and radiographic features in these cases are consistent with hypertrophic osteopathy, secondary to pregnancy. This is the first report describing presumptive hypertrophic osteopathy in takin.


Assuntos
Doenças Ósseas/veterinária , Período Periparto , Ruminantes , Animais , Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/etiologia , Doenças Ósseas/patologia , Feminino , Membro Anterior/diagnóstico por imagem , Membro Anterior/patologia , Membro Posterior/diagnóstico por imagem , Membro Posterior/patologia , Gravidez
8.
J Craniofac Surg ; 30(6): 1760-1763, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31261317

RESUMO

BACKGROUND: While the risk for intracranial extension of midline nasoglabellar dermoid cysts is well-described, the risk in non-midline dermoid cysts and role of preoperative imaging in these lesions is less understood. This study aims to address this gap and provide preoperative recommendations. MATERIALS AND METHODS: A retrospective review was performed evaluating patients who underwent excision of craniofacial dermoid cysts by a single surgeon. Findings on preoperative physical examination and imaging modalities were compared to intraoperative findings to assess effectiveness of each in predicting bony erosion. A treatment algorithm is proposed. RESULTS: Twenty-eight patients were included and 50% had intraoperatively confirmed bony erosion. Bony erosion was identified in 100% of lesions immobile on examination, compared to 30% of mobile lesions (P = 0.001). Bony erosion was identified in 40.9% of lateral brow cysts compared to 83.3% of lesions located elsewhere (P = 0.03), in 60% of patients with periorbital sequelae compared to 47.8% without periorbital sequelae, and in 66.7% of patients with reported change in cyst size with Valsalva compared to 48.0% without change with Valsalva. Sensitivities for preoperative identification of bony erosion were as follows: physical examination 57.1%, US 11.1%, MRI 66.7%, and CT 100%. CONCLUSIONS: A management algorithm for non-midline dermoid cysts is presented. CT or MRI is recommended for lesions that are immobile, in atypical locations, or have associated periorbital sequelae or change with Valsalva. The authors feel there is no role for ultrasound and don't recommend routine imaging in patients with non-midline dermoid cysts without features suggestive of bony erosion.


Assuntos
Doenças Ósseas/diagnóstico por imagem , Cisto Dermoide/diagnóstico por imagem , Crânio/diagnóstico por imagem , Doenças Ósseas/etiologia , Criança , Pré-Escolar , Cisto Dermoide/complicações , Cisto Dermoide/cirurgia , Feminino , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Estudos Retrospectivos
9.
Minerva Urol Nefrol ; 71(5): 445-456, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31353876

RESUMO

INTRODUCTION: In the last years, there have been significant developments in the therapeutic armamentarium of metastatic castration-resistant prostate cancer (mCRPC). New evidence shows that the addition of bone-targeted agents (BTA) to "life-prolonging agents" result in improved clinical benefit. This review aims to give an overview of data for the use of BTAs in a new era of mCRPC where new agents are used in daily practice. EVIDENCE ACQUISITION: A non-systematic review of the literature was performed combining the keywords: "castration-resistant prostate cancer" and "bone-targeted therapy". The primary objective was to provide a critical assessment of data for the use of BTAs in mCRPC, and the secondary objective was to assess novel targeted therapy. EVIDENCE SYNTHESIS: Zoledronic acid and denosumab have shown to be effective in reducing the risk of SREs in patients with mCRPC. The point at which treatment with bisphosphonates or denosumab should be initiated during PCa evolution has yet to be determined. The EMA has restricted the usage of Ra-223 to patients who have had two previous treatments for mCRPC to the bone or who cannot receive other treatments. Ra-223 should only be used as monotherapy or in combination with ADT for the treatment of mCRPC, symptomatic bone metastases and without visceral metastases. With recent developments in PSMA-targeted radiopharmaceuticals, PSMA RLT agents are now under investigation for the treatment of mCRPC. CONCLUSIONS: Reducing skeletal-related morbidity remains a crucial goal of palliative life-extending therapy in mCRPC. New data about dosing schedules and combinations of different treatments will continue to refine the optimal strategy for incorporating BTAs into the new treatment paradigms for PCa. Novel molecules such as PSMA-targeted small molecules promise theranostic agents in the management of PCa patients.


Assuntos
Antineoplásicos/uso terapêutico , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/etiologia , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Osso e Ossos/efeitos dos fármacos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Sistemas de Liberação de Medicamentos , Humanos , Masculino
10.
Animal ; 13(12): 2932-2938, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31155019

RESUMO

Vitamins play an essential role in broiler nutrition. They are fundamental for normal metabolic and physiological process, and their requirements for poultry are not fixed and can be affected by multiple factors. In contrast, mycotoxins are a challenging issue because they hinder performance and the immune system. Vitamin supplementation above minimum requirements would permit improvement in productive potential, health, bone and meat quality in a situation of mycotoxin challenge. The objective of this study was to determine the influence of optimum vitamin nutrition in diets contaminated with aflatoxin in broilers from 1 to 44 days of age. A total of 1800 Cobb 500 male chicks were randomized to 15 sets of eight treatment groups, each containing 15 birds using a 2 × 2 × 2 factorial design (commercial vitamin levels and high vitamin levels, two levels of aflatoxin - 0 and 0.5 ppm with binder levels of 0 and 10 000 mg/kg). The mash diets were corn and soybean meal based, formulated according to commercial practices. Feed intake, weight gain and feed conversion were analyzed for birds from 1 to 44 days of age. To determine carcass characteristics (carcass yield, breast yield and leg yield) and black bone syndrome, two birds were slaughtered from each group at 45 days. Other analyses included breast tenderness, water loss by dripping and malonaldehyde concentrations. The results demonstrated that broilers that were fed high levels of vitamins showed better weight gain, feed conversion, carcass yield and breast yield than broilers that were fed diets with commercial vitamin levels (P < 0.05); also, broilers that were fed diets containing 0.5 ppm aflatoxin had lower weight gain, carcass yield and breast yield (P < 0.05). The use of 10 000 mg/kg of binder improved (P < 0.05) feed conversion throughout the rearing period. We conclude that aflatoxin negatively affects performance and carcass yield; however, feeding optimum vitamin nutrition improved these performance traits.


Assuntos
Aflatoxinas/efeitos adversos , Doenças Ósseas/veterinária , Galinhas , Carne/análise , Doenças das Aves Domésticas/epidemiologia , Vitaminas/metabolismo , Aflatoxinas/administração & dosagem , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Doenças Ósseas/epidemiologia , Doenças Ósseas/etiologia , Brasil/epidemiologia , Galinhas/crescimento & desenvolvimento , Galinhas/fisiologia , Dieta/veterinária , Suplementos Nutricionais/análise , Masculino , Doenças das Aves Domésticas/etiologia , Distribuição Aleatória , Vitaminas/administração & dosagem
11.
Rev Esp Cir Ortop Traumatol ; 63(4): 253-260, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31147299

RESUMO

BACKGROUND: Recently, a new approach of autologous chondrocyte implantation technique (using as biomaterial a collagen type i/iii membrane) based on increasing cell density called HD-ACI (High Density Autologous Chondrocyte Implantation) has been described. The objective of this paper was to study the clinical outcome and incidence of subchondral bone oedema in patients with cartilage lesions in the knee treated with HD-ACI at 1-2 years of follow-up. METHODS: This is a retrospective study performed with forty patients with chondral injuries grade iii-iv. All patients were treated with HD-ACI with a cellular dose of 5×106 chondrocytes /cm2 of lesion. The subjective perception of improvement of symptoms and functionality was measured with the IKDC score (International Knee Documentation Committee). The presence of bone oedema was assessed at 6, 12 and 24 months of follow-up by magnetic resonance imaging. RESULTS: IKDC values showed a significant improvement at 12 and 24 months (P<.001). The mean difference of IKDC between the baseline visit and 12 months was 26.3 points, and 31.6 points at 24 months. Twenty-seven point five percent of the patients presented subchondral bone oedema at 2 years of follow-up. CONCLUSIONS: HD-ACI is an effective and safe treatment that improves pain, clinical perception and functionality of the joint. No correlation was found between the presence of bone oedema and the patients' clinical outcome.


Assuntos
Doenças Ósseas/etiologia , Condrócitos/transplante , Edema/etiologia , Articulação do Joelho/cirurgia , Complicações Pós-Operatórias/etiologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos
12.
Int J Mol Sci ; 20(12)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216696

RESUMO

Mastocytosis is a hematopoietic neoplasm defined by abnormal expansion and focal accumulation of clonal tissue mast cells in various organ-systems. The disease exhibits a complex pathology and an equally complex clinical behavior. The classification of the World Health Organization (WHO) divides mastocytosis into cutaneous forms, systemic variants, and localized mast cell tumors. In >80% of patients with systemic mastocytosis (SM), a somatic point mutation in KIT at codon 816 is found. Whereas patients with indolent forms of the disease have a normal or near-normal life expectancy, patients with advanced mast cell neoplasms, including aggressive SM and mast cell leukemia, have a poor prognosis with short survival times. In a majority of these patients, multiple somatic mutations and/or an associated hematologic neoplasm, such as a myeloid leukemia, may be detected. Independent of the category of mastocytosis and the serum tryptase level, patients may suffer from mediator-related symptoms and/or osteopathy. Depending on the presence of co-morbidities, the symptomatology in such patients may be mild, severe or even life-threatening. Most relevant co-morbidities in such patients are IgE-dependent allergies, psychiatric, psychological or mental problems, and vitamin D deficiency. The diagnosis and management of mastocytosis is an emerging challenge in clinical practice and requires vast knowledge, a multidisciplinary approach, and personalized medicine procedures. In this article, the current knowledge about mastocytosis is reviewed with special emphasis on the multidisciplinary aspects of the disease and related challenges in daily practice.


Assuntos
Mastocitose/diagnóstico , Mastocitose/terapia , Medicina de Precisão , Anafilaxia/etiologia , Biomarcadores , Doenças Ósseas/diagnóstico , Doenças Ósseas/etiologia , Medula Óssea/patologia , Gerenciamento Clínico , Humanos , Imunoglobulina E/imunologia , Mastócitos/imunologia , Mastócitos/metabolismo , Mastócitos/patologia , Mastocitose/complicações , Mastocitose/etiologia , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/etiologia , Mastocitose Sistêmica/terapia , Mutação , Medicina de Precisão/métodos , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Risco , Índice de Gravidade de Doença
13.
Int J Paleopathol ; 26: 48-60, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31228793

RESUMO

OBJECTIVE: To carefully assess skeletal lesions in close environment context in order to evaluate whether skeletal fluorosis was present in individuals living in the prehistoric Midwest, USA. MATERIALS: Skeletal remains from minimally 117 individuals recovered from the Ray Site, located in western Illinois (USA) and dated to the Middle/early Late Woodland periods (50 BC-AD 400). METHODS: Macroscopic evaluation of all recovered skeletal elements. RESULTS: Eight individuals display a constellation of abnormal bony changes, including osteosclerosis, a high frequency of fractures, and dental abnormalities. CONCLUSIONS: The osteosclerotic changes along with the naturally high fluoride content of west central Illinois soil and water suggests the presence of skeletal fluorosis. SIGNIFICANCE: This is the first report of skeletal fluorosis from archaeologically recovered human remains from North America. LIMITATIONS: The ambiguous nature of the skeletal changes associated with fluorosis, especially in the less severe stages of the disease, renders determination of the etiology difficult. SUGGESTIONS FOR FURTHER RESEARCH: The continuation of paleopathological investigations of fluoride toxicity within archaeological communities recovered from this region with emphasis on the incorporation of biomedical and environmental data. Furthermore, complementary analyses of the chemical composition and the histological presentation of the skeletons could provide support for this diagnosis.


Assuntos
Doenças Ósseas/etiologia , Doenças Ósseas/história , Exposição Ambiental/história , Intoxicação por Flúor/história , Doenças Ósseas/patologia , Criança , Feminino , Intoxicação por Flúor/patologia , Fluorose Dentária/história , Fluorose Dentária/patologia , História Antiga , Humanos , Illinois , Masculino , Pessoa de Meia-Idade , Paleopatologia
14.
J Med Econ ; 22(8): 766-776, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30969797

RESUMO

Aim: The approved indication for denosumab (120 mg) was expanded in 2018 to include skeletal-related event (SRE) prevention in patients with multiple myeloma (MM). Therefore, a cost-effectiveness analysis was conducted comparing denosumab with zoledronic acid (ZA) for SRE prevention in patients with MM from the national healthcare system perspective in a representative sample of European countries: Austria, Belgium, Greece, and Italy. Methods: The XGEVA global economic model for patients with MM was used to calculate incremental cost-effectiveness ratios (ICERs) for denosumab vs ZA over a lifetime horizon. Clinical inputs were derived from the denosumab vs ZA randomized, phase 3 study ("20090482") in patients newly-diagnosed with MM, and comprised real-world adjusted SRE rates, serious adverse event (SAE) rates, treatment duration, dose intensity, progression-free survival (PFS), and overall survival (OS). Economic inputs comprised country-specific denosumab and ZA acquisition and administration costs, SRE and SAE management costs, and discount rates. Health utility decrements associated with MM disease progression, SRE and SAE occurrence, and route of administration were included. Results: Estimated ICERs (cost per quality-adjusted life-year [QALY] gained) for denosumab vs ZA in Austria, Belgium, Greece, and Italy were €26,294, €17,737, €6,982, and €27,228, respectively. Using 1-3 times gross domestic product (GDP) per capita per QALY as willingness to pay thresholds, denosumab was 69-94%, 84-96%, 79-96%, and 50-92% likely to be cost-effective vs ZA, respectively. Limitations: Economic inputs were derived from various sources, and time to event inputs were extrapolated from 20090482 study data. Conclusions: Denosumab is cost-effective vs ZA for SRE prevention in patients with MM in Austria, Belgium, Greece, and Italy, based on often-adopted World Health Organization thresholds. This conclusion is robust to changes in model parameters and assumptions. Cost-effectiveness estimates varied across the four countries, reflecting differences in healthcare costs and national economic evaluation guidelines.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas/tratamento farmacológico , Doenças Ósseas/etiologia , Denosumab/uso terapêutico , Mieloma Múltiplo/complicações , Ácido Zoledrônico/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/economia , Análise Custo-Benefício , Denosumab/efeitos adversos , Denosumab/economia , Relação Dose-Resposta a Droga , Esquema de Medicação , Europa (Continente) , Gastos em Saúde , Humanos , Cadeias de Markov , Modelos Econômicos , Mieloma Múltiplo/mortalidade , Anos de Vida Ajustados por Qualidade de Vida , Análise de Sobrevida , Ácido Zoledrônico/efeitos adversos , Ácido Zoledrônico/economia
15.
Artif Organs ; 43(10): 988-1001, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30932185

RESUMO

Coronary artery calcifications (CACs) are common among maintenance hemodialysis (MHD) patients and associated with increased morbidity and mortality due to cardiovascular events. The insight into chronic kidney disease-mineral and bone disorder (CKD-MBD) established a correlation between dysregulated mineral metabolism and CACs. This study aimed to identify the association of mineral content outside of bone (MCOB) with CACs and cardiovascular events in MHD patients. In the pilot prospective study with no intervention, patients underwent body composition assessment by body composition monitor after hemodialysis and computed tomography examination using the Agatston scoring method simultaneously within a week. The primary end point included cardiovascular events and cardiovascular death. Correlations and receiver operating characteristic analysis elucidated the associations of MCOB with CACs; multivariate analysis assessed the cardiovascular risk for groups with different MCOB. One hundred three eligible patients with an average age of 48 (35-63) years old were enrolled and followed up to 12 (11-12.5) months, among which 52.4% had detectable CACs at baseline. MCOB showed an inverse correlation with Agatston score and significantly discriminated the patients with Agatston score > 0 (AUC = 0.737; P < 0.001) and 400 (AUC = 0.733; P < 0.001). MCOB ≤ 9.2657 mg/kg was an independent risk factor for CACs (OR = 4.853; P = 0.044) and strong predictor for cardiovascular morbidity and mortality (HR = 10.108; P = 0.042), as well as rehospitalization (HR = 2.689; P = 0.004). MCOB inversely correlated with the presence and extent of CACs, and could discriminate Agatston score > 0 and 400, which also presented as an independent indicator for CKD-MBD and 1-year cardiovascular prognosis in adult MHD patients. Additional studies are required for identifying this issue.


Assuntos
Cálcio/análise , Minerais/análise , Diálise Renal , Insuficiência Renal Crônica/complicações , Calcificação Vascular/etiologia , Adulto , Idoso , Composição Corporal , Doenças Ósseas/diagnóstico , Doenças Ósseas/etiologia , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Resultado do Tratamento , Calcificação Vascular/diagnóstico
16.
Artigo em Inglês | MEDLINE | ID: mdl-30918438

RESUMO

Objective: We aimed to investigate the musculoskeletal and pulmonary outcomes of patients with osseous sarcoidosis. Methods: We identified 24 patients with osseous sarcoidosis and at least one year of follow-up after diagnosis (baseline). We collected outcome data at 1-year follow-up and last follow-up. We defined a composite outcome measure; worsening considered as worsening in any of the following 4 components compared to baseline: 1) osseous sarcoidosis symptoms, 2) musculoskeletal imaging of affected bone, 3) chest imaging, or 4) pulmonary function testing (PFT). Results: A minority of patients had a worsening composite outcome at 1-year (9/24, 38%) and last follow-up (5/24, 21%). When only considering musculoskeletal symptoms and imaging, only 25% (6/24) and 13% (3/24) of patients worsened compared to baseline at 1-year and last follow-up, respectively. Patients with a worsening composite overall outcome tended to be older at baseline than those without the outcome for both 1-year (54.3 years vs. 47.5 years, p=0.11) and last follow-up (55.0 years vs. 48.7 years; p=0.23), although these differences were non-significant. Treatment was not associated with worsening composite overall outcome at 1-year follow-up (p=0.40), but was significantly associated with decreased risk for worsening at last follow-up (p=0.05). Conclusions: In this retrospective cohort study of osseous sarcoidosis, most patients had a favorable outcome according to symptoms, musculoskeletal/chest imaging, and PFTs, even though only a minority were treated with glucocorticoids or DMARDs. These results suggest that the natural history of osseous sarcoidosis is often benign, although some patients experience clinical progression.


Assuntos
Doenças Ósseas/etiologia , Sarcoidose Pulmonar/etiologia , Sarcoidose/complicações , Adulto , Fatores Etários , Antirreumáticos/uso terapêutico , Doenças Ósseas/diagnóstico , Doenças Ósseas/tratamento farmacológico , Progressão da Doença , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento
18.
Int Wound J ; 16(4): 916-924, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30916475

RESUMO

Autologous bone grafting is the gold standard in patients with bone defects but is associated with significant pain and donor site morbidity. Autologous lipotransfer (fat grafting or lipofilling) has become very popular in the therapy of chronic wounds. Mesenchymal stem cells from adipose tissue are known for their regenerative, reparative, and immunomodulatory effects. This case study and review evaluates the use of autologous lipotransfer for chronic osteomyelitis in a 26-year-old patient. A 26-year-old female suffering from chronic tibial osteomyelitis was initially treated with surgical debridement and antibiotics followed by lipoharvest and autologous lipofilling. MRI and computed tomography scans were performed at 2 and 6 weeks and 6 months postoperatively. A formal systematic review of clinical trials investigating autologous lipotransfer for osteomyelitis was conducted. The patient remained asymptomatic without recurrence, and the bone defect cavity showed vascularised adipose tissue after 6 weeks, with early signs of osteogenesis. The highest foot and ankle disability index was 100. The systematic review identified 266 studies after duplicates were removed. After screening for eligibility, seven manuscripts were further assessed, with none meeting the inclusion criteria. This is the first study to report the successful use of autologous lipotransfer with early signs of osteogenesis in a patient suffering from chronic osteomyelitis. Autologous lipotransfer is relatively simple, safe, and minimally invasive, making it a potential alternative to current treatments. Further research is required to assess the safety, feasibility, and efficacy of autologous fat grafting and the mechanism of osteogenesis.


Assuntos
Tecido Adiposo/transplante , Doenças Ósseas/etiologia , Doenças Ósseas/terapia , Osteomielite/complicações , Procedimentos Cirúrgicos Reconstrutivos/métodos , Transplante Autólogo/métodos , Adulto , Feminino , Humanos , Resultado do Tratamento
19.
BMJ Case Rep ; 12(3)2019 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-30904884

RESUMO

We report a case of a woman who was admitted with a suspicion of metastatic malignancy of unknown primary origin. A few months prior to her admission, she presented to a rheumatologist with acute anterior uveitis, psoriasiform rashes and polyarthritis. A diagnosis of psoriatic arthropathy was made and she was treated accordingly. Soon after she presented with persistent back and right upper quadrant abdominal pain for which she had a CT scan done with evidence of hilar lymphadenopathy, liver hypodensities and lytic-sclerotic bone lesions. She was referred to our hospital for further investigations and management. After re-exploring her clinical presentation and further investigations (including a liver biopsy), a diagnosis of multisystemic sarcoidosis with ocular, reticuloendothelial, hepatic and skeletal involvement was made. The patient was started on systemic glucocorticoids and second line immunosuppressants and demonstrated significant clinical improvement with resolution of her liver granulomata on imaging and improvement in her back pain. The case illustrates the importance of a thorough clinical assessment, review of investigations and an open mind in the evaluation of a patient.


Assuntos
Glucocorticoides/uso terapêutico , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Dor Abdominal/etiologia , Doenças Ósseas/etiologia , Diagnóstico Diferencial , Oftalmopatias/etiologia , Feminino , Granuloma/etiologia , Humanos , Hepatopatias/etiologia , Pessoa de Meia-Idade , Sistema Fagocitário Mononuclear/fisiopatologia , Sarcoidose/complicações
20.
Blood ; 133(14): 1534-1539, 2019 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-30760454

RESUMO

Bone disease is a cardinal complication of multiple myeloma that affects quality of life and survival. Osteocytes have emerged as key players in the development of myeloma-related bone disease. Along with other factors, they participate in increased osteoclast activity, decreased osteoblast function, and immunosuppressed marrow microenvironment, which deregulate bone turnover and result in bone loss and skeletal-related events. Denosumab is a novel alternative to bisphosphonates against myeloma bone disease. Special considerations in this constantly evolving field are thoroughly discussed.


Assuntos
Doenças Ósseas/tratamento farmacológico , Mieloma Múltiplo/complicações , Doenças Ósseas/etiologia , Denosumab/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico , Osteócitos/patologia
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